Nicotinamide adenine dinucleotide, NAD+, is the single most important coenzyme you've probably never heard of. It shows up in roughly 500 enzymatic reactions across the human body, and without it, the electron-transport chain that produces cellular energy simply stops working.
What NAD+ actually does
NAD+ is a coenzyme, meaning it doesn't do work on its own, it partners with enzymes to make reactions happen. Its main job is to carry electrons. When your mitochondria convert fuel (glucose, fat, amino acids) into ATP, they do it by stripping electrons from those molecules and handing them off through a chain of carriers. NAD+ is one of the most critical of those carriers.
Beyond energy production, NAD+ is the substrate for three enzyme families that govern how well your cells maintain themselves:
- Sirtuins, sometimes called the "longevity enzymes," sirtuins regulate DNA repair, gene expression, and metabolic flexibility. They require NAD+ to function.
- PARPs, poly(ADP-ribose) polymerases fix DNA damage. Every repair they perform consumes NAD+.
- CD38, an NADase that degrades NAD+ during immune responses. CD38 activity rises sharply with age, which is part of why levels decline.
Why levels drop with age
By middle age, tissue NAD+ levels are typically 50% lower than they were in your twenties. Several things happen simultaneously: CD38 expression rises, chronic low-grade inflammation increases PARP activity, and biosynthesis of new NAD+ slows down. The result is a supply-and-demand mismatch, your cells need NAD+ for more repair work than ever, and they're making less of it.
The decline isn't linear. Most studies show the steepest drop between ages 40 and 60, with smaller reductions before and after.
Why you can't just take NAD+
Oral NAD+ itself is poorly bioavailable. The molecule is too large and charged to cross cell membranes efficiently, and most of it gets broken down in the gut before it can be used. This is why the research has focused on precursors, smaller molecules the body can assemble into NAD+ inside the cell, where it's actually needed.
The two precursors that matter
NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are the two most studied NAD+ precursors. Both work, both have published human data, and both raise NAD+ levels, though through slightly different pathways. We break down the research in detail in NMN vs NR: Choosing Your NAD+ Precursor.
The short version
NAD+ is cellular currency. You spend it on energy production and repair work, and as you age the supply tightens while the demand grows. Replenishing the precursors is one of the few longevity interventions with real human data behind it, which is why it's become the foundation of most serious cellular health protocols.